EP2655361B1 - Process for the preparation of triazinyl substituted oxindoles - Google Patents

Description

The present application relates to improved processes for the preparation of triazinyl-substituted oxindoles and their use as intermediates for the synthesis of fine chemicals and of active ingredients in agriculture.

Oxindoles substituted in the 3-position represent an important structural motif in a number of natural substances and pharmaceutically active substances. Some of these compounds exhibit biological activity against various clinical pictures and have, for example, antitumor or anti-HIV properties ( Ding et al., J. Med. Chem. 2006, 49, 3432 ; Jiang et al., Bioorg. Med. Chem. Lett. 2006, 16, 2105 ).

Another subgroup of the 3-position heteroaromatic substituted oxindoles are the 3-triazinyloxindoles (3- (1,3,5-triazin-2-yl) -1,3-dihydro-2H-indol-2-ones , with the trivial name referred to as "3-Triazinyloxindole" compounds, is the subject of the present invention.

It is known that a hydrogen bound to an aromatic, heteroaromatic or to an aliphatic carbon skeleton can be exchanged for functional substituents, which may also be aromatic, heteroaromatic or aliphatic.

Interestingly, the reaction conditions for the substitution of hydrogen in the 3-position of oxindoles, depending on the nature of the substituents, are different. Accordingly, the reaction conditions for the exchange for aliphatic, aromatic and heteroaromatic radicals were independently investigated and developed.

Standard substitution reactions of oxindoles in the 3-position include the replacement of hydrogen with aliphatic substituents ( Science of Synthesis, 10 (2000), p.600 ).

The replacement of aromatic substituents in the presence of palladium was by Taylor et al. (J. Am. Chem. Soc., 2009, 131, 9900-9901 ), such as by Altman et al. (J. Am. Chem. Soc. 2008, 130 (29), 9613-9620 ) such as by Durbin et al. (Org. Lett., 2008, 10 (7), 1413-1415 ).

The synthesis of substituted oxindoles in which the hydrogen has been replaced by heteroaromatic 6-membered ring substituents is also described. Exemplified here are the substitution in the 3-position of N-methyloxindole with a substituted pyridazine ( Shen et al., Org. Lett., 2006, 8, 1447-1450 ), the preparation of substituted 3- (quinazolin-4-yl) -oxindoles ( US 6265411 ), the substitution in the 3-position of oxindole with substituted quinazolines on a solid phase ( Hennequin et al., Tetrahedron Lett., 1999, 40, 3881-3884 ), substitution with substituted pyridines or pyridine N-oxides (eg.

US 2009/291982 . WO 2007/89193 . WO 2005/27823 . WO 2003/82853 ), the preparation of substituted 3- (pyrimidin-4-yl) -oxindoles ( WO 2006/136606 . WO 2003/82853 . US 2007/281949 ) or the preparation of substituted 3- (2H-pyrazolo [3,4-d] pyrimidin-4-yl) -oxindoles ( US 2007/281949 ).

According to Scheme 1, 3-triazinyloxindoles can be obtained by replacing a 3-position hydrogen atom of an optionally substituted oxindole (1) with an optionally substituted triazine (2) carrying a suitable leaving group X in the presence of a "suitable" base.

It is known that the step of deprotonation of the oxindole, which is important for the exchange of hydrogen, can be specifically influenced by the choice of the substituent R ³ .

The reactions disclosed in the aforementioned prior art have in common that the oxindole used is first deprotonated with a strong base and then the heterocyclic component, typically as a chlorine compound, is added.

Deprotonation in the art strong, water-sensitive bases, such as Natriumhexamethyldilsilazan or lithium diisopropylamide (LDA), sodium hydride or lithium hydride, are used.

Disadvantageously, the use of the bases sodium hydride and lithium hydride leads to the formation of equimolar amounts of elemental hydrogen. In addition, the solvents used in connection with these bases must be dried consuming prior to their use.

An analogous coupling - analogous to the one in WO 2005/061519 described coupling of oxindoles with quinolines, in the quinoline-N-oxides in the presence of Acetic anhydride are used - with triazines of the formula (2) is not known.

In Scheme 2 is summarized a known method for the preparation of substituted 3-Triazinyloxindolen. These are characterized in that they carry on the triazine nitrogen substituent. The synthesis is in US 2004/116388 . WO 2002/083654 and WO 2001/025220 disclosed.

As the triazine-containing component, a substituted 4-chloro-N-phenyl-1,3,5-triazin-2-amine was used in the reaction according to Scheme 2. The reaction was carried out by deprotonation of the oxindole used in DMF / THF with sodium hydride, followed by the addition of the triazine component and subsequent stirring of the reaction mixture at 80.degree.

Disadvantageously, the yields obtained in this known synthesis are only 2.5%, or 7% for the unsubstituted nitrogen at the nitrogen (R ² = H) and 29% for the N-Methyloxindol (R ² = Me).

The disadvantages of the method described relate, in addition to the very low Yields, including the use of strong bases such as sodium hydride, which lead to the formation of equimolar amounts of elemental hydrogen, which are technically difficult to handle. Therefore, the method described is not a viable solution for the technical (industrial) scale.

In the in US 2004/116388 For the preparation of substituted 3-triazinyloxindoles described for compound number 380, only 0.4 equivalents of the triazine component is used per equivalent of the oxindole component. Based on the oxindole component, this can only lead to a maximum theoretical yield of 40%. An increase in the yield can be achieved by using an excess of oxindole. Since the oxindole component, depending on the substitution pattern, may be the more valuable educt, this reaction procedure using a 2.5-fold excess of oxindole on an industrial scale is to be regarded as disadvantageous.

It has already been pointed out that the reaction conditions for the replacement of the hydrogen in the 3-position of oxindoles with aliphatic, aromatic and heteroaromatic substituents had to be established independently of each other, because the nature of the substituents to be introduced can greatly influence the reaction.

The same again appears for the further branching, i. the further substitution of these substituents, in particular for the further substitution of the heteroaromatic substituents to apply.

Thus, in the prior art, no technically suitable synthesis of 3-Triazinyloxindolen which carry on the triazine ring alkyl or Alkoxysubstituenten described.

The use of hitherto known preparation processes in the synthesis of 3-triazinyloxindoles which carry alkyl or alkoxy substituents on the triazine ring, does not provide satisfactory results on a technical (industrial) scale.

For comparison purposes, those in the document US 2004/116388 described conditions in the reaction of 7-fluoro-1,3-dihydro-2H-indol-2-one (Example 1 variant F), or 1,3-dihydro-2H-indol-2-one (Example 2 variant B ) with 2-chloro-4,6-dimethoxy-1,3,5-triazine.

It was found that the yields obtained, in each case based on the oxindole component only 39% (Example 1 variant F), or only 34% (Example 2 variant B) are. If these conditions are used in the reaction of the starting materials in a technically advantageous ratio, namely 1 equivalent of the oxindole component with 1.2 equivalents of the triazine component, then the yields obtained are 39% (Example 1 variant G) and 30% (Example 2) Variant C).

In Organic Letters (2010) 2306-2309 In the arylation reactions described in Table 4, 3-phenyloxindole is used in each case as educt, ie an oxindole which carries a phenyl substituent in the 3-position. This 3-phenyloxindole is arylated with electron-poor chlorobenzene derivatives and 5-halooxazoles in the presence of cesium carbonate in the 3-position.

As is known, the acidity of methyl groups or methylene groups is generally greatly increased by replacing a hydrogen substituent with a phenyl substituent. This leads to a pKa value of the remaining hydrogen substituent on the methyl group or methylene group which is lowered by several orders of magnitude.

In a number of publications, there are corresponding examples in which pKa values of organic or inorganic compounds in water or in organic solvents such as dimethyl sulfoxide are described. The pKa values in organic solvents were either measured directly or over others Methods extrapolated. So is in Acc. Chem. Res. 1988, 21, 456 in Table II for 4-methylpyridine a pKa of 35 (extrapolated for DMSO) and for 4-benzylpyridine a pKa of 26.7 (in DMSO) are given. Also in Acc. Chem. Res. 1988, 21, 456 in Table 11, for (methylsulfanyl) benzene, a pKa of 42 (extrapolated for DMSO), for (benzylsulfanyl) benzene a pKa of 30.8 (in DMSO) and for diphenylmethylphenylsulfide a pKa of 26.8 (in DMSO ). For oxindole is in Acc. Chem. Res. 1988, 21, 456 in Table II a pKa value of 18.2 (in DMSO) is given.

In the examples mentioned, the increase in the acidity of methyl groups or methylene groups by several orders of magnitude by exchanging a hydrogen substituent for a phenyl substituent very clear.

In the examples of the present application, only oxindoles were used as starting materials, which carry two hydrogen atoms in the 3-position. In Organic Letters (2010) 2306-2309 on the other hand, 3-phenyloxindoles are used as starting materials. The educts thus differ in their acidity. Oxindoles, which carry two hydrogen atoms in the 3-position, are less acidic than those in Organic Letters (2010) 2306-2309 in the reactions of Table 4 used 3-Phenyloxindol.

Not surprisingly, in the literature examples which describe arylation reactions on 3-unsubstituted oxindoles, strong bases such as sodium hydride are used. The fact that even for oxindoles which carry a substituent in the 3-position, which reduces the acidity by several orders of magnitude in nonaqueous solvents, weaker bases such as cesium carbonate can be used for the deprotonation was to be expected for the skilled person and has been described in Organic Letters (2010) 2306-2309 approved.

However, it is surprising to those skilled in the art that according to the teachings of the invention, an arylation reaction at 3-position unsubstituted oxindoles (Oxindoles which have two hydrogens in the 3-position) is unexpectedly possible with weaker bases such as potassium carbonate or sodium hydroxide in good yields.

To the applicability of in Organic Letters (2010) 2306 (Supplement Page S-12 General Procedure) for the arylation of 3-aryloxindoles with electron-poor chlorobenzene derivatives and 5-halooxazoles (Table 4 in Organic Letters (2010) 2306 ) even when using chlorotriazines, 3-phenyl-1,3-dihydro-2H-indol-2-one was treated with 2-chloro-4,6-dimethoxy-1,3,5-triazine in the presence of cesium carbonate in N, N-dimethylformamide reacted (see Example 10). Since the reaction was very rapid even at room temperature, was waived an increased temperature and a prolonged reaction time. The product contained in the reaction mixture was purified by column chromatography. However, structure elucidation by 2D NMR confirms that the product obtained is not the desired 3-position arylated product (3- (4,6-dimethoxy-1,3,5-triazin-2-yl) -3 -phenyl-1,3-dihydro-2H-indol-2-one) but the O-arylated product (2 - [(4,6-dimethoxy-1,3,5-triazin-2-yl) oxy] 3-phenyl-1H-indole).

Subsequently, for comparison purposes, the in Organic Letters (2010) 2306 (Supplement Page S-12 General Procedure) also used arylation using chlorotriazines to arylate a 3-unsubstituted oxindole. For this purpose, 7-fluoro-1,3-dihydro-2H-indol-2-one was reacted with 2-chloro-4,6-dimethoxy-1,3,5-triazine in the presence of cesium carbonate in N, N-dimethylformamide (Example 1 variant H). However, as the reaction product, the 3-position arylated title compound was obtained in only 22% yield. The main products obtained in the isolated solid and in the concentrated mother liquor were several times arylated products. It was also shown by HPLC analysis that the oxindole used as starting material had not completely reacted.

Thus, that is in Organic Letters (2010) 2306 (Supplement page S-12 General Procedure) described methods not suitable to produce 3-Triazinyloxindole on an industrial scale, at least when 2-chloro-4,6-dimethoxy-1,3,5-triazine is used as Arylierungsreagenz.

Against this background, the object of the invention is to provide an improved process which, on an industrial scale, makes it possible to produce 3-triazinyloxindoles in a simplified manner compared to the known processes while at the same time improving the overall yield.

Surprisingly, it has now been found that the weaker bases potassium carbonate or sodium carbonate and lithium hydroxide, sodium hydroxide, potassium hydroxide, barium hydroxide or Tertalkylammoniumhydroxid, and potassium phosphate (K ₃ PO ₄ ), K ₂ HPO ₄ or sodium phosphate or mixtures consisting of at least two of the aforementioned bases to the solution suitable for the task.

The abovementioned bases have the advantage that they are suitable for use on an industrial scale, since they are not decomposable, in particular in the presence of water, and do not produce equimolar amounts of hydrogen and at the same time lead to a significantly improved overall yield.

worin
R^1a bis R^1d unabhängig voneinander ausgewählt sind aus der Gruppe bestehend aus Wasserstoff, Fluor, Chlor, Brom, lod sowie aus
(C₁-C₆)-Alkyl, wobei der Alkylrest verzweigt oder unverzweigt ist und unsubstituiert ist oder durch einen oder mehrere Substituenten, ausgewählt aus der aus Fluor, Chlor, (C₁-C₄)-Alkoxy oder (C₃-C₇)-Cycloalkyl bestehenden Gruppe, substituiert ist,
(C₃-C₈)-Cycloalkyl, wobei der Cycloalkylrest unsubstituiert ist oder durch einen oder mehrere Substituenten, ausgewählt aus der aus Fluor, Chlor, (C₁-C₄)-Alkyl oder (C₃-C₇)-Cycloalkyl oder (C₁-C₄)-Alkoxy bestehenden Gruppe, substituiert ist,
(C₁-C₆)-Alkoxy, wobei der Alkoxyrest verzweigt oder unverzweigt ist und unsubstituiert ist oder durch einen oder mehrere Substituenten, ausgewählt aus der aus Fluor, Chlor, (C₁-C₄)-Alkoxy oder (C₃-C₇)-Cycloalkyl bestehenden Gruppe, substituiert ist,
(C₃-C₇)-Cycloalkoxy, wobei der Cycloalkoxyrest unsubstituiert ist oder durch einen oder mehrere Substituenten, ausgewählt aus der aus Fluor, Chlor, (C₁-C₄)-Alkyl oder (C₁-C₄)-Alkoxy bestehenden Gruppe, substituiert ist,
(C₁-C₆)-Alkylthio, wobei der Alkylthiorest verzweigt oder unverzweigt ist und unsubstituiert ist oder durch einen oder mehrere Substituenten, ausgewählt aus der aus Fluor, Chlor, (C₁-C₄)-Alkyl oder (C₁-C₄)-Alkoxy bestehenden Gruppe, substituiert ist,
(C₃-C₇)-Cycloalkylthio, wobei der Cycloalkylthiorest unsubstituiert ist oder durch einen oder mehrere Substituenten, ausgewählt aus der Fluor, Chlor, (C₁-C₄)-Alkyl oder (C₁-C₄)-Alkoxy bestehenden Gruppe, substituiert ist, und Phenyl oder 1-Naphthyl oder 2-Naphthyl oder ein fünf- oder sechsgliedriger heteroaromatischer Ring mit 1 bis 2 Heteroatomen, wobei die Heteroatome unabhängig voneinander ausgewählt sind, aus der Gruppe bestehend aus O oder N und wobei der Aryl- oder Heteroarylrest unsubstituiert ist oder durch einen oder mehrere Substituenten, ausgewählt aus der aus Fluor, Chlor, Brom, lod, (C₁-C₄)-Alkyl, (C₁-C₄)-Alkoxy oder (C₃-C₇)-Cycloalkyl oder (C₁-C₄)-Alkylthio bestehenden Gruppe, substituiert ist, und
R² für
Wasserstoff,
(C₁-C₆)-Alkyl, wobei der Alkylrest unsubstituiert ist oder durch einen oder mehrere Substituenten, ausgewählt aus der aus Fluor, Chlor, (C₁-C₄)-Alkoxy oder (C₃-C₇)-Cycloalkyl bestehenden Gruppe, substituiert ist, oder
Benzyl, wobei das Benzyl unsubstituiert ist oder substituiert ist durch einen oder mehrere Substituenten, ausgewählt aus der Gruppe bestehend aus Fluor, Chlor, Brom, lod, Nitro, (C₁-C₄)-Alkyl, (C₁-C₄)-Alkoxy oder (C₃-C₇)-Cycloalkyl oder (C₁-C₄)-Alkylthio sowie aus COOR^a, worin R^a für ein (C₁-C₄)-Alkyl steht, und -CONR^b'R^b" oder -CONHR^b"worin R^b' und R^b" jeweils unabhängig voneinander für ein (C₁-C₄)-Alkyl steht, wobei jeweils zwei Substituenten am N-Atom zusammen gegebenenfalls einen unsubstituierten oder substituierten Ring bilden,
steht,
R³ für Wasserstoff oder Methyl,
steht,
R⁴ und R⁵ unabhängig voneinander jeweils für
Wasserstoff,
(C₁-C₆)-Alkyl, wobei der Alkylrest unsubstituiert ist oder durch einen oder mehrere Substituenten, ausgewählt aus der aus Fluor, Chlor, (C₁-C₄)-Alkoxy oder (C₃-C₇)-Cycloalkyl bestehenden Gruppe, substituiert ist,
(C₁-C₆)-Alkoxy, wobei der Alkoxyrest verzweigt oder unverzweigt ist und unsubstituiert ist oder durch einen oder mehrere Substituenten, ausgewählt aus der aus Fluor, Chlor, (C₁-C₄)-Alkoxy oder (C₃-C₇)-Cycloalkyl bestehenden Gruppe, substituiert ist,
stehen,
wobei ein Oxindol (1)

worin
R^1a bis R^1d sowie R² und R³ wie in Formel (3) definiert sind, in einem Lösungsmittel umgesetzt wird mit einem Triazin (2)

worin
R⁴ und R⁵ wie in Formel (3) definiert sind, und
X als Abgangsgruppe für Cl, Br, I, Alkoxy, Alkylsulfonyl, (Alkylsulfonyl)oxy, Haloalkylsulfonyl, Phenylsulfonyl oder Toluol-4-Sulfonyl steht, dadurch gekennzeichnet, dass die Umsetzung in Gegenwart von

• Kaliumcarbonat oder Natriumcarbonat,
• Lithiumhydroxid, Natriumhydroxid, Kaliumhydroxid, Bariumhydroxid oder Tertalkylammoniumhydroxid,
• Kaliumphosphat (K₃PO₄), Kaliumhydrogenphosphate (K₂HPO₄) oder Natriumphosphat, oder
• in einer mindestens zwei der vorgenannten Basen umfassenden Mischung erfolgt.

Thus, the object is achieved by a process for the preparation of compounds of the formula (3)

wherein
R ^1a to R ^{1d are} independently selected from the group consisting of hydrogen, fluorine, chlorine, bromine, iodine and from
(C ₁ -C ₆ ) -alkyl, wherein the alkyl radical is branched or unbranched and is unsubstituted or by one or more substituents selected from among fluorine, chlorine, (C ₁ -C ₄ ) -alkoxy or (C ₃ -C ₇ ) -cycloalkyl-substituted group, is substituted,
(C ₃ -C ₈ ) -cycloalkyl, wherein the cycloalkyl radical is unsubstituted or by one or more substituents selected from among fluorine, chlorine, (C ₁ -C ₄ ) -alkyl or (C ₃ -C ₇ ) -cycloalkyl or (C ₁ -C ₄ ) -alkoxy group, is substituted,
(C ₁ -C ₆ ) -Alkoxy, wherein the alkoxy radical is branched or unbranched and is unsubstituted or by one or more substituents selected from among fluorine, chlorine, (C ₁ -C ₄ ) alkoxy or (C ₃ -C ₇ ) -cycloalkyl-substituted group, is substituted,
(C ₃ -C ₇₎ cycloalkoxy, wherein the cycloalkoxy group is unsubstituted or existing by one or more substituents selected from the group consisting of fluorine, chlorine, (C ₁ -C ₄₎ -alkyl or (C ₁ -C ₄₎ alkoxy Group, is substituted,
(C ₁ -C ₆ ) -Alkylthio, wherein the alkylthio radical is branched or unbranched and is unsubstituted or by one or more substituents selected from among fluorine, chlorine, (C ₁ -C ₄ ) alkyl or (C ₁ -C ₄ ) alkoxy-substituted group, is substituted,
(C ₃ -C ₇ ) -cycloalkylthio, wherein the cycloalkylthio radical is unsubstituted or by one or more substituents selected from the group consisting of fluoro, chloro, (C ₁ -C ₄ ) -alkyl or (C ₁ -C ₄ ) -alkoxy is substituted, and phenyl or 1-naphthyl or 2-naphthyl or a five- or six-membered heteroaromatic ring having 1 to 2 heteroatoms, wherein the heteroatoms are independently selected from the group consisting of O or N and wherein the aryl or Heteroaryl radical is unsubstituted or by one or more substituents selected from among fluorine, chlorine, bromine, iodine, (C ₁ -C ₄ ) -alkyl, (C ₁ -C ₄ ) -alkoxy or (C ₃ -C ₇ ) - Cycloalkyl or (C ₁ -C ₄ ) -alkylthio existing group, is substituted, and
R ² for
Hydrogen,
(C ₁ -C ₆ ) -alkyl, wherein the alkyl radical is unsubstituted or by one or more substituents selected from among fluorine, chlorine, (C ₁ -C ₄ ) -alkoxy or (C ₃ -C ₇ ) -cycloalkyl Group, is substituted, or
Benzyl, where the benzyl is unsubstituted or substituted by one or more substituents selected from the group consisting of fluorine, chlorine, bromine, iodine, nitro, (C ₁ -C ₄ ) -alkyl, (C ₁ -C ₄ ) - Alkoxy or (C ₃ -C ₇ ) -cycloalkyl or (C ₁ -C ₄ ) -alkylthio and also from COOR ^a , in which R ^{a is} a (C ₁ -C ₄ ) -alkyl, and -CONR ^{b '} R ^{b "} or -CONHR ^{b "wherein} R ^{b 'and} R ^b' each independently represents a (C ₁ -C ₄₎ -alkyl, where each of two substituents on the nitrogen atom optionally form together an unsubstituted or substituted ring,
stands,
R ^{3 is} hydrogen or methyl ,
stands,
R ⁴ and R ⁵ are each independently
Hydrogen,
(C ₁ -C ₆ ) -alkyl, wherein the alkyl radical is unsubstituted or by one or more substituents selected from among fluorine, chlorine, (C ₁ -C ₄ ) -alkoxy or (C ₃ -C ₇ ) -cycloalkyl Group, is substituted,
(C ₁ -C ₆ ) -Alkoxy, wherein the alkoxy radical is branched or unbranched and is unsubstituted or by one or more substituents selected from among fluorine, chlorine, (C ₁ -C ₄ ) alkoxy or (C ₃ -C ₇ ) -cycloalkyl-substituted group, is substituted,
stand,
where an oxindole (1)

wherein
R ^1a to R ^1d and R ² and R ^{3 are} as defined in formula (3), is reacted in a solvent with a triazine (2)

wherein
R ⁴ and R ^{5 are} as defined in formula (3), and
X is a leaving group for Cl, Br, I, alkoxy, alkylsulfonyl, (alkylsulfonyl) oxy, haloalkylsulfonyl, phenylsulfonyl or toluene-4-sulfonyl, characterized in that the reaction in the presence of

• Potassium carbonate or sodium carbonate,
• Lithium hydroxide, sodium hydroxide, potassium hydroxide, barium hydroxide or tert-alkyl ammonium hydroxide,
• Potassium phosphate (K ₃ PO ₄ ), potassium hydrogen phosphate (K ₂ HPO ₄ ) or sodium phosphate, or
• in a mixture comprising at least two of the aforementioned bases.

worin die Reste R^1a bis R^1d, R² und R³ wie oben definiert sind, sind bekannt oder können unter Anwendung der dem Fachmann bekannten Verfahren hergestellt werden. Soweit in dieser Anmeldung auf ein "Triazin" oder eine "Triazinkomponente" verwiesen wird, ist eine der von der allgemeinen Formel (2) umfassten Verbindungen gemeint. Die ebenfalls als Edukte eingesetzten Triazine (2)

worin R⁴, R⁵ und X wie oben definiert sind, sind ebenfalls bekannt oder können unter Anwendung von dem Fachmann bekannten Verfahren hergestellt werden.As far as reference is made in this application to an "oxindole", it is meant one of the compounds encompassed by the general formula (1). The oxindoles used as starting materials (1)

wherein the radicals R ^1a to R ^1d , R ² and R ^{3 are} as defined above, are known or can be prepared using the methods known in the art. As far as reference is made in this application to a "triazine" or a "triazine component", it is meant one of the compounds encompassed by the general formula (2). The triazines (2) also used as starting materials

wherein R ⁴ , R ⁵ and X are as defined above are also known or can be prepared using methods known to those skilled in the art.

With regard to the compounds according to the invention, the terms used above and below are summarized. These are familiar to the person skilled in the art and in particular have the meanings explained below:

The term "halogen" means, for example, fluorine, chlorine, bromine or iodine. When the term for a group is used, "halogen" means, for example, a fluorine, chlorine, bromine or iodine atom.

Alkyl is a straight-chain or branched, open-chain, saturated hydrocarbon radical.

The term "(C ₁ -C ₄ ) alkyl" denotes a short notation for alkyl having one to 4 carbon atoms corresponding to the range indicated for C atoms, ie the radicals methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, 2-butyl, 2-methylpropyl or tert-butyl. General alkyl radicals having a larger specified range of carbon atoms, eg. B. "(C ₁ -C ₆ ) alkyl", correspondingly also include straight-chain or branched alkyl radicals having a larger number of carbon atoms, ie according to Example, the alkyl radicals having 5 and 6 carbon atoms.

Cycloalkyl means a carbocyclic saturated ring system preferably having 3-8 ring C atoms, e.g. Cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

In the case of substituted cycloalkyl, spirocyclic aliphatic systems are also included, such as spiro [2.2] pent-1-yl, spiro [2.3] hex-1-yl, spiro [2.3] hex-4-yl, 3-spiro [2.3] hex-5-yl.

Aryl is a mono-, bi- or polycyclic aromatic system having preferably 6 to 14, in particular 6 to 10 ring C atoms, for example phenyl, naphthyl, anthryl, phenanthrenyl, and the like, preferably phenyl.

The term "optionally substituted aryl" also includes polycyclic systems, such as tetrahydronaphthyl, indenyl, indanyl, fluorenyl, biphenylyl, where the binding site is on the aromatic system.

As a rule, aryl is also encompassed by the term "optionally substituted phenyl".

Alkoxy is an alkyl radical bonded via an oxygen atom, alkenyloxy is an alkynyl radical bonded via an oxygen atom, alkynyloxy is an alkynyl radical bound via an oxygen atom, cycloalkyloxy is a cycloalkyl radical bonded via an oxygen atom, and cycloalkenyloxy is a cycloalkenyl radical bonded via an oxygen atom.
Alkylthio means an alkyl radical bonded via a sulfur atom, alkenylthio means an alkenyl radical bonded via a sulfur atom, alkynylthio means an alkynyl radical bonded via a sulfur atom, cycloalkylthio means a cycloalkyl radical bonded via a sulfur atom and cycloalkenylthio means a cycloalkenyl radical bonded via a sulfur atom.

Haloalkyl, alkenyl and alkynyl mean, by identical or different halogen atoms, partially or completely substituted alkyl, alkenyl or alkynyl, for example monohaloalkyl (= monohaloalkyl), such as CH ₂ CH ₂ Cl, CH ₂ CH ₂ F, CHClCH ₃ , CHFCH ₃ , CH ₂ Cl, CH ₂ F; Perhaloalkyl such as CCl ₃ or CF ₃ or CF ₂ F ₃ ; Polyhaloalkyl such as CHF ₂ , CH ₂ F, CH ₂ CHFCl, CHCl ₂ , CF ₂ CF ₂ H, CH ₂ CF ₃ ; Haloalkoxy is, for example, OCF ₃ , OCHF ₂ , OCH ₂ F, OCF ₂ CF ₃ , OCH ₂ CF ₃ and OCH ₂ CH ₂ Cl; The same applies to haloalkenyl and other halogen-substituted radicals.

Unless defined otherwise, the definition "substituted by one or more radicals" means, independently of one another, one or more identical or different radicals, it being possible for two or more radicals to form one or more rings on one cycle as main body.

The respectively unsubstituted or substituted radicals may be branched and unbranched. Thus, for example, a group designated "C ₄ alkyl" includes In addition to the unbranched butyl radical, all other C ₄ isomers including tert- butyl.

If two or more radicals form one or more rings, these may be carbocyclic, heterocyclic, saturated, partially saturated, unsaturated, for example also aromatic and optionally further substituted. The fused rings are preferably 5- or 6-membered rings, particularly preferred are benzo-fused rings.

The core of the process according to the invention is the reaction of the starting materials of the formula (1) and (2) in the presence of bases, which are not decomposed in the presence of water and, in addition, no hydrogen (H ₂ ) release.

Some very strong to medium strong bases, e.g. Sodium hydride (NaH), reacting in water with decomposition and are therefore not suitable for industrial application. Bases with these disadvantages are safe to handle only on a laboratory scale. For the technical, i. industrial, application are strong bases, such as NaH, therefore not suitable.

• Kaliumcarbonat oder Natriumcarbonat, sowie
• Lithiumhydroxid, Natriumhydroxid, Kaliumhydroxid, Bariumhydroxid oder Tertalkylammoniumhydroxid, sowie
• Kaliumphosphat (K₃PO₄), K₂HPO₄ oder Natriumphosphat, oder
• Mischungen aus mindestens zwei der vorgenannten Basen.

In the inventive reaction can be used as a base

• Potassium carbonate or sodium carbonate, as well
• Lithium hydroxide, sodium hydroxide, potassium hydroxide, barium hydroxide or Tertalkylammoniumhydroxid, and
• Potassium phosphate (K ₃ PO ₄ ), K ₂ HPO ₄ or sodium phosphate, or
• Mixtures of at least two of the aforementioned bases.

The carbonates, hydroxides and phosphates mentioned have the substantial advantage over strong bases, such as, for example, sodium hydride, that they are technically (industrially) more suitable, since their use does not involve any equimolar amounts Hydrogen are formed and said weaker bases do not decompose in the presence of water.

Particularly preferred bases are potassium carbonate, sodium carbonate, sodium hydroxide, potassium hydroxide or an at least two-component mixture consisting of at least one of the two carbonates: potassium carbonate and sodium carbonate and at least one of the two hydroxides: potassium hydroxide or sodium hydroxide.

The four particularly preferred two-component mixtures thus relate to the mixtures consisting of potassium carbonate and potassium hydroxide, potassium carbonate and sodium hydroxide, sodium carbonate and potassium hydroxide and the mixture consisting of potassium carbonate and sodium hydroxide.

In addition, of course, other mixtures are conceivable, each containing more than two of the above as the reaction particularly preferred bases.

However, since the bases used according to the invention contain, or can generate or release water, triazines (2) readily hydrolyze in the presence of water, it must be regarded as surprising that the bases used in accordance with the invention could prove suitable for achieving the object.

In a preferred embodiment of the process according to the invention, the radicals R ^1a to R ^1d in the compounds of the formulas (3) and (1) are independently selected from the group consisting of hydrogen, fluorine, chlorine, bromine, iodine and also
(C ₁ -C ₆ ) -alkyl, wherein the alkyl radical is branched or unbranched and is unsubstituted or substituted by one or more substituents selected from the group consisting of fluorine and chlorine, and
(C ₃ -C ₇ ) -cycloalkyl, wherein the cycloalkyl radical is unsubstituted or by one or more substituents selected from among fluorine, chlorine, (C ₁ -C ₄ ) -alkyl or (C ₃ -C ₇ ) -cycloalkyl or (C ₁ -C ₄ ) -alkoxy existing group, is substituted.

In a particularly preferred embodiment, the radicals R ^1a to R 1 ^d in the compounds of the formulas (3) and (1) are independently selected from the group consisting of fluorine, chlorine and trifluoromethyl (CF ₃ ), trifluoromethoxy (O-CF ₃ ) and methoxy (O-Me).

In a very particularly preferred embodiment, the radical R ^{1a is} fluorine or chlorine, ie the compounds of the formulas (3) and (1) are substituted in the 7-position by fluorine (7-fluoro) or chlorine (7-chloro).

Also very particularly preferred are compounds of the formulas (3) and (1) which are substituted in the 5-position by fluorine (5-fluoro), ie the radical R ^1c is fluorine (see Example 5).

Very particular preference is also given to compounds of the formulas (3) and (1) which are substituted in the 7-position by fluorine (7-fluoro) and at the same time in the 5-position by fluorine (5-fluoro), ie the radicals R ^1a and R ^1c are fluorine (see Example 3).

• Wasserstoff, oder für jeweils
• unsubstituiertes Methyl, Ethyl und Benzyl.

In a further particularly preferred embodiment, the radical R ² in the formulas (3) and (1) stands for

• Hydrogen, or for each
• unsubstituted methyl, ethyl and benzyl.

In a very particularly preferred embodiment, the nitrogen in the 1-position of the compounds of the formulas (3) and (1) is unsubstituted, ie the radical R ² is hydrogen.

In the context of the invention, it is preferred that the reaction mixture from which the product of formula (3) with R ³ = H can be obtained by adding acid or a mixture of acids, in particular hydrochloric acid, sulfuric acid, acetic acid or formic acid, in a technically relevant concentration, made acidic, then the organic solvent is distilled off completely or partially and the residue is filtered. The solid product thus obtained can be washed with suitable solvents.

Furthermore, it is particularly preferred that the reaction mixture from which the product of formula (3) with R ³ = H can be obtained acidified by the addition of hydrochloric acid or sulfuric acid of a technically relevant concentration, acetic acid or formic acid, and additionally another organic solvent Add and the residue is filtered. The solid product thus obtained can be washed with suitable solvents.

It is within the scope of the invention that to the reaction mixture containing products of formula (3), before or during acidification, a suitable amount of defoamer is added to reduce undesirable foaming of the reaction mixture.

In a particularly preferred embodiment, the radicals R ⁴ and R ⁵ in the formulas (2) and (3) are each independently unsubstituted (C ₁ -C ₄ ) -alkyl, and unsubstituted (C ₁ -C ₄ ) -alkoxy.

Very particular preference is given to compounds of the formulas (2) and (3) in which the radicals R ⁴ and R ^{5 are} each independently of one another methoxy, ethoxy, methyl, ethyl.

In a particularly preferred embodiment, the leaving group X is a chlorine.

• einem polaren, oder
• einem unpolaren Lösungsmittel, oder in
• einem Gemisch aus einem polaren oder unpolaren Lösungsmittel durchgeführt werden.

An important aspect concerns the selection of the solvent in which the reaction is carried out. The implementation can be in

• a polar, or
• a nonpolar solvent, or in
• a mixture of a polar or nonpolar solvent.

• Haloalkane, insbesondere Dichlormethan oder Dichlorethan; oder
• Aromaten, insbesondere Toluol, Xylol oder Chlorbenzol,
  verwendet werden.

As non-polar solvents can

• Haloalkanes, in particular dichloromethane or dichloroethane; or
• Aromatics, in particular toluene, xylene or chlorobenzene,
  be used.

• Ketone, insbesondere Aceton, Butanon, 2-Methylbutanon;
• Nitrile, insbesondere Acetonitril, Butyronitril, Isobutylnitril;
• Amide, insbesondere N,N-Dimethylformamid, N,N-Dimethylacetamid, Formamid, N-Methylformamid, N-Methylpyrrolidon;
• Sulfoxide und Sulfone, zum Beispiel Dimethylsulfoxid, Dimethlysulphone, Sulfolan;
• Ether, insbesondere Dioxan, 2-Methyltetrahydrofuran, Methylcyclopentylether, tert-Butylmethylether oder Tetrahydrofuran; oder
• Ester, insbesondere Ethylacetat, n-Butylacetat oder Isopropylacetat verwendet werden.

As polar organic solvents can

• Ketones, in particular acetone, butanone, 2-methylbutanone;
• Nitriles, in particular acetonitrile, butyronitrile, isobutylnitrile;
• Amides, in particular N, N-dimethylformamide, N, N-dimethylacetamide, formamide, N-methylformamide, N-methylpyrrolidone;
• Sulfoxides and sulfones, for example dimethyl sulfoxide, dimethly sulphone, sulfolane;
• Ethers, in particular dioxane, 2-methyltetrahydrofuran, methylcyclopentyl ether, tert-butylmethyl ether or tetrahydrofuran; or
• Ester, especially ethyl acetate, n-butyl acetate or isopropyl acetate can be used.

The stated polar solvents can be used either alone or in mixtures with other solvents, preferably with further polar organic solvents or with water. It is not excluded that the reaction takes place in water as the sole solvent.

It is particularly preferred to carry out the process without the use of water as solvent.

The process of the invention for preparing compounds of formula (3) is based on reacting the oxindole (1 equivalent) in a suitable solvent with the triazine component and the base. The triazine component is preferably used in excess (1.1 to 1.4 equivalents, preferably 1.1 to 1.25 equivalents).

The base is used equimolar or in excess. When R ² = H, the base is used at 2 to 3 equivalents, preferably at 2.2 to 2.6 equivalents.

All reactants may be premixed either in pure form or with each other or dissolved or suspended in a solvent or solvent mixture to the reaction mixture.

For good product yields, it has been found that it may be advantageous to first react the oxindole with the base (total or subset) in a suitable solvent and then the triazine component and optionally an additional amount of the same or another base or mixture various bases added in one or more portions

Another addition variant is that the oxindole and the triazine component are initially introduced in a suitable solvent and the base, or the mixture of different bases, is added in portions.

The addition of the reactants can take place in one portion or in several portions over a period of up to 24 hours, preferably up to 6 hours, in particular 0.05 to 6 hours.

The reaction temperature is in the range of -20 ° C to 150 ° C, preferably in the range -10 ° C to 90 ° C.

Optionally, the reaction can be carried out under pressure.

Additional solvent may be added during the reaction to allow for better mixing of the reactants.

Depending on the reaction conditions used, the stirring time after addition of all the reactants is in the range up to 48 hours, preferably 0.05 to 24 hours.

Work-up and isolation of the desired product of formula (3) may be accomplished in various ways, for example, depending on which solvent is used or whether the product is a solid or a liquid.

welche beispielsweise durch das oben beschriebene erfindungsgemäße Verfahren erhältlich sind, und deren Salze (3"),

worin jeweils
R^1a bis R^1d unabhängig voneinander ausgewählt sind aus der Gruppe bestehend aus Wasserstoff, Fluor, Chlor, Brom, Iod sowie aus
(C₁-C₆)-Alkyl, wobei der Alkylrest verzweigt oder unverzweigt ist und unsubstituiert ist oder durch einen oder mehrere Substituenten, ausgewählt aus der aus Fluor, Chlor, (C₁-C₄)-Alkoxy oder (C₃-C₇)-Cycloalkyl bestehenden Gruppe, substituiert ist,
(C₃-C₈)-Cycloalkyl, wobei der Cycloalkylrest unsubstituiert ist oder durch einen oder mehrere Substituenten, ausgewählt aus der aus Fluor, Chlor, (C₁-C₄)-Alkyl oder (C₃-C₇)-Cycloalkyl oder (C₁-C₄)-Alkoxy bestehenden Gruppe, substituiert ist,
(C₁-C₆)-Alkoxy, wobei der Alkoxyrest verzweigt oder unverzweigt ist und unsubstituiert ist oder durch einen oder mehrere Substituenten, ausgewählt aus der aus Fluor, Chlor, (C₁-C₄)-Alkoxy oder (C₃-C₇)-Cycloalkyl bestehenden Gruppe, substituiert ist,
(C₃-C₇)-Cycloalkoxy, wobei der Cycloalkoxyrest unsubstituiert ist oder durch einen oder mehrere Substituenten, ausgewählt aus der aus Fluor, Chlor, (C₁-C₄)-Alkyl oder (C₁-C₄)-Alkoxy bestehenden Gruppe, substituiert ist,
(C₁-C₆)-Alkylthio, wobei der Alkylthiorest verzweigt oder unverzweigt ist und unsubstituiert ist oder durch einen oder mehrere Substituenten, ausgewählt aus der aus Fluor, Chlor, (C₁-C₄)-Alkyl oder (C₁-C₄)-Alkoxy bestehenden Gruppe, substituiert ist,
(C₃-C₇)-Cycloalkylthio, wobei der Cycloalkylthiorest unsubstituiert ist oder durch einen oder mehrere Substituenten, ausgewählt aus der Fluor, Chlor, (C₁-C₄)-Alkyl oder (C₁-C₄)-Alkoxy bestehenden Gruppe, substituiert ist, und Phenyl oder 1-Naphthyl oder 2-Naphthyl oder ein fünf- oder sechsgliedriger heteroaromatischer Ring mit 1 bis 2 Heteroatomen, wobei die Heteroatome unabhängig voneinander ausgewählt sind, aus der Gruppe bestehend aus O oder N und wobei der Aryl- oder Heteroarylrest unsubstituiert ist oder durch einen oder mehrere Substituenten, ausgewählt aus der aus Fluor, Chlor, Brom, lod, (C₁-C₄)-Alkyl, (C₁-C₄)-Alkoxy oder (C₃-C₇)-Cycloalkyl oder (C₁-C₄)-Alkylthio bestehenden Gruppe, substituiert ist, und
R² für
Wasserstoff,
(C₁-C₆)-Alkyl, wobei der Alkylrest verzweigt oder unverzweigt ist und unsubstituiert ist oder durch einen oder mehrere Substituenten, ausgewählt aus der aus Fluor, Chlor, (C₁-C₄)-Alkoxy oder (C₃-C₇)-Cycloalkyl bestehenden Gruppe, substituiert ist, oder
Benzyl, wobei das Benzyl unsubstituiert ist oder substituiert ist durch einen oder mehrere Substituenten, ausgewählt aus der Gruppe bestehend aus Fluor, Chlor, Brom, lod, Nitro, (C₁-C₄)-Alkyl, (C₁-C₄)-Alkoxy oder (C₃-C₇)-Cycloalkyl oder (C₁-C₄)-Alkylthio sowie aus COOR^a, worin R^a für ein (C₁-C₄)-Alkyl steht, und -CONR^b'R^b" oder-CONHR^b" worin R^b' und R^b" jeweils unabhängig voneinander für ein (C₁-C₄)-Alkyl steht, wobei jeweils zwei Substituenten am N-Atom zusammen gegebenenfalls einen unsubstituierten oder substituierten Ring bilden,
steht,
R³ für
Wasserstoff oder Methyl
steht,
R⁴ und R⁵ unabhängig voneinander jeweils für
Wasserstoff,
(C₁-C₆)-Alkyl, wobei der Alkylrest unsubstituiert ist oder durch einen oder mehrere Substituenten, ausgewählt aus der aus Fluor, Chlor, (C₁-C₄)-Alkoxy oder (C₃-C₇)-Cycloalkyl bestehenden Gruppe, substituiert ist, (C₁-C₆)-Alkoxy, wobei der Alkoxyrest verzweigt oder unverzweigt ist und unsubstituiert ist oder durch einen oder mehrere Substituenten, ausgewählt aus der aus Fluor, Chlor, (C₁-C₄)-Alkoxy oder (C₃-C₇)-Cycloalkyl bestehenden Gruppe, substituiert ist,
stehen,
wobei in den Salzen der allgemeinen Formel (3")
M für Li, Na, K, N(R^c)₄, mit R^c = H oder C₁-C₆ Alkyl, Cs, Ba, Mg, Ca und Zn steht und die Anzahl der Gegenionen M⁺ sich nach der jeweiligen Ladung richtet, so dass eine insgesamt neutrale Verbindung der allgemeinen Formel (3") entsteht.The invention also relates to the compounds of the formula (3),

which are obtainable, for example, by the process according to the invention described above, and salts thereof (3 "),

in each case
R ^1a to R ^{1d are} independently selected from the group consisting of hydrogen, fluorine, chlorine, bromine, iodine and from
(C ₁ -C ₆ ) -alkyl, wherein the alkyl radical is branched or unbranched and is unsubstituted or by one or more substituents selected from among fluorine, chlorine, (C ₁ -C ₄ ) -alkoxy or (C ₃ -C ₇ ) -cycloalkyl-substituted group, is substituted,
(C ₃ -C ₈ ) -cycloalkyl, wherein the cycloalkyl radical is unsubstituted or by one or more substituents selected from among fluorine, chlorine, (C ₁ -C ₄ ) -alkyl or (C ₃ -C ₇ ) -cycloalkyl or (C ₁ -C ₄ ) -alkoxy group, is substituted,
(C ₁ -C ₆ ) -Alkoxy, wherein the alkoxy radical is branched or unbranched and is unsubstituted or by one or more substituents selected from among fluorine, chlorine, (C ₁ -C ₄ ) alkoxy or (C ₃ -C ₇ ) -cycloalkyl-substituted group, is substituted,
(C ₃ -C ₇ ) -cycloalkoxy, wherein the cycloalkoxy radical is unsubstituted or by one or more substituents selected from among fluorine, chlorine, (C ₁ -C ₄ ) -alkyl or (C ₁ -C ₄ ) -alkoxy Group, is substituted,
(C ₁ -C ₆ ) -Alkylthio, wherein the alkylthio radical is branched or unbranched and is unsubstituted or by one or more substituents selected from among fluorine, chlorine, (C ₁ -C ₄ ) alkyl or (C ₁ -C ₄ ) alkoxy-substituted group, is substituted,
(C ₃ -C ₇ ) -Cycloalkylthio, wherein the cycloalkylthio is unsubstituted or by one or more substituents selected from the fluoro, chloro, (C ₁ -C ₄ ) alkyl or (C ₁ -C ₄ ) alkoxy group, and phenyl or 1-naphthyl or 2-naphthyl or a five- or six-membered heteroaromatic ring having 1 to 2 heteroatoms, wherein the heteroatoms are independently selected from A group consisting of O or N and wherein the aryl or heteroaryl radical is unsubstituted or by one or more substituents selected from among fluorine, chlorine, bromine, iodine, (C ₁ -C ₄ ) -alkyl, (C ₁ -C ₄ ) -Alkoxy or (C ₃ -C ₇ ) -cycloalkyl or (C ₁ -C ₄ ) -alkylthio existing group, and
R ² for
Hydrogen,
(C ₁ -C ₆ ) -alkyl, wherein the alkyl radical is branched or unbranched and is unsubstituted or by one or more substituents selected from among fluorine, chlorine, (C ₁ -C ₄ ) -alkoxy or (C ₃ -C ₇ ) -cycloalkyl-substituted group, or is substituted
Benzyl, where the benzyl is unsubstituted or substituted by one or more substituents selected from the group consisting of fluorine, chlorine, bromine, iodine, nitro, (C ₁ -C ₄ ) -alkyl, (C ₁ -C ₄ ) - Alkoxy or (C ₃ -C ₇ ) -cycloalkyl or (C ₁ -C ₄ ) -alkylthio and also from COOR ^a , in which R ^{a is} a (C ₁ -C ₄ ) -alkyl, and -CONR ^{b '} R ^{b "} or -CONHR ^{b "} wherein R ^{b '} and R ^b" each independently represent a (C ₁ -C ₄ ) -alkyl, wherein in each case two substituents on the N-atom together optionally form an unsubstituted or substituted ring,
stands,
R ³ for
Hydrogen or methyl
stands,
R ⁴ and R ⁵ are each independently
Hydrogen,
(C ₁ -C ₆ ) -alkyl, wherein the alkyl radical is unsubstituted or by one or more substituents selected from among fluorine, chlorine, (C ₁ -C ₄ ) -alkoxy or (C ₃ -C ₇ ) -cycloalkyl Group, is substituted, (C ₁ -C ₆ ) -Alkoxy, wherein the alkoxy radical is branched or unbranched and is unsubstituted or by one or more substituents selected from among fluorine, chlorine, (C ₁ -C ₄ ) alkoxy or (C ₃ -C ₇ ) -cycloalkyl-substituted group, is substituted,
stand,
wherein in the salts of the general formula (3 ")
M is Li, Na, K, N ( ^Rc ) ₄ , with R ^c = H or C ₁ -C ₆ alkyl, Cs, Ba, Mg, Ca and Zn and the number of counterions M ⁺ depending on the particular charge so that a total neutral compound of the general formula (3 ") is formed.

The formulas (3) and (3 ") also include, as appropriate, all stereoisomers, tautomers and / or polymorphic forms and salts thereof.

Particular preference is given to compounds of the general formulas (3) in which R ^{3 is} H or methyl.

Most preferred are compounds of the general formulas (3) in which R ^{3 is} H.

Compounds of the general formulas (3) and (3 ") and the compounds of the general formula (3) prepared by the process according to the invention are suitable as intermediates for the preparation of fine chemicals and active ingredients from agriculture.

Compounds of the formula (3) and (3 ") are triazinyl-substituted oxindoles. In Scheme 3 below, triazinyl-substituted oxindoles are designated by the formula (5-1).

Scheme 3 shows a novel multi-step synthesis method according to which, starting from a 3- (alkylsulfanyl) -1,3-dihydro-2H-indol-2-one of the formula (7-1) in a total of five-step reaction, an N-alkyl N- [2- (1,3,5-triazin-2-ylcarbonyl) phenyl] alkanesulfonamide of the formula (4-1), the herbicidal (see WO 2007/031208 A2 ) and fungicidal (see WO 2006/008159 A1 ) Activity has long been known, can be produced.

• Reduktion von substituierten oder unsubstituierten 3-(Alkylsulfanyl)-1,3-dihydro-2H-indol-2-onen (7-1) zu substituierten oder unsubstituierten 1,3-Dihydro-2H-indol-2-onen (6-1). Dieses Verfahren ist im technischen Maßstab möglich und ist in der Patentanmeldung mit der Anmeldenummer EP 10162381.7 beschrieben.
• Arylierung von substituierten oder unsubstituierten 1,3-Dihydro-2H-indol-2-onen (6-1) zu triazinylsubstituierten Oxindolen (5-1). Dieses Verfahren ist im technischen Maßstab möglich und ist in der vorliegenden Patentanmeldung beschrieben.
• Sulfonylierung von triazinylsubstituierten Oxindolen (5-1) zu N-sulfonylsubstituierten 3-Triazinyloxindolen (2-1). Dieses Verfahren ist im technischen Maßstab möglich und ist in der Patentanmeldung mit der Anmeldenummer EP 111598751 beschrieben.
• Oxidative Ringöffnung von N-sulfonylsubstituierten 3-Triazinyloxindolen (2-1) zu 2-(Triazinylcarbonyl)sulfonaniliden (1-1). Dieses Verfahren ist im technischen Maßstab möglich und ist in der Patentanmeldung mit der Anmeldenummer DE 102011086382.6 beschrieben.
• Alkylierung von 2-(Triazinylcarbonyl)sulfonaniliden (1-1) zu N-Alkyl-N-[2-(1,3,5-triazin-2-ylcarbonyl)phenyl]alkansulfonamiden (4-1). Dieses Verfahren ist in der Patentanmeldung mit der Anmeldenummer WO 2006/008159 beschrieben.

The multi-step process for the preparation of N-alkyl-N- [2- (1,3,5-triazin-2-ylcarbonyl) phenyl] alkanesulfonamides (4-1) consists of the following substeps:

• Reduction of substituted or unsubstituted 3- (alkylsulfanyl) -1,3-dihydro-2H-indol-2-ones (7-1) to substituted or unsubstituted 1,3-dihydro-2H-indol-2-ones (6-1 ). This method is possible on an industrial scale and is in the patent application with the application number EP 10162381.7 described.
• Arylation of substituted or unsubstituted 1,3-dihydro-2H-indol-2-ones (6-1) to triazinyl-substituted oxindoles (5-1). This method is possible on an industrial scale and is described in the present patent application.
• Sulfonylation of triazinyl-substituted oxindoles (5-1) to give N-sulfonyl-substituted 3-triazinyloxindoles (2-1). This method is possible on an industrial scale and is in the patent application with the application number EP 111598751 described.
• Oxidative ring opening of N-sulfonyl-substituted 3-triazinyloxindoles (2-1) to 2- (triazinylcarbonyl) sulfonanilides (1-1). This method is possible on an industrial scale and is in the patent application with the application number DE 102011086382.6 described.
• Alkylation of 2- (triazinylcarbonyl) sulfonanilides (1-1) to N-alkyl-N- [2- (1,3,5-triazin-2-ylcarbonyl) phenyl] alkanesulfonamides (4-1). This method is in the patent application with the application number WO 2006/008159 described.

The new multi-step process shown in Scheme 3 is distinguished from the previously known processes for the preparation of N-alkyl-N- [2- (1,3,5-triazin-2-ylcarbonyl) phenyl] alkanesulfonamides (4-1) and also 2 - (Triazinylcarbonyl) sulfonanilides (1-1) characterized in that oxindole compounds are used as starting materials or as intermediates. This has the advantage that it can be carried out in comparison to the previously known methods on an industrial scale and at the same time high yields can be obtained.

1. A)Verfahren zur Herstellung von N-Alkyl-N-[2-(1,3,5-triazin-2-ylcarbonyl)phenyl]alkansulfonamiden der Formel (4-1)
   
   worin
   R^1a bis R^1d unabhängig voneinander ausgewählt sind aus der Gruppe bestehend aus Wasserstoff, Fluor, Chlor, Brom, lod sowie aus
   (C₁-C₆)-Alkyl, wobei der Alkylrest unsubstituiert ist oder durch einen oder mehrere Substituenten, ausgewählt aus der aus Fluor, Chlor, (C₁-C₄)-Alkoxy oder (C₃-C₇)-Cycloalkyl bestehenden Gruppe, substituiert ist,
   (C₃-C₇)-Cycloalkyl, wobei der Cycloalkylrest unsubstituiert ist oder durch einen oder mehrere Substituenten, ausgewählt aus der aus Fluor, Chlor, (C₁-C₄)-Alkyl oder (C₃-C₇)-Cycloalkyl oder (C₁-C₄)-Alkoxy bestehenden Gruppe, substituiert ist,
   (C₁-C₆)-Alkoxy, wobei der Alkoxyrest unsubstituiert ist oder durch einen oder mehrere Substituenten, ausgewählt aus der aus Fluor, Chlor, (C₁-C₄)-Alkoxy
   oder (C₃-C₇)-Cycloalkyl bestehenden Gruppe, substituiert ist, (C₃-C₇)-Cycloalkoxy, wobei der Cycloalkoxyrest unsubstituiert ist oder durch einen
   oder mehrere Substituenten, ausgewählt aus der aus Fluor, Chlor, (C₁-C₄)-Alkyl oder (C₁-C₄)-Alkoxy bestehenden Gruppe, substituiert ist, (C₁-C₆)-Alkylthio, wobei der Alkylthiorest unsubstituiert ist oder durch einen oder mehrere Substituenten, ausgewählt aus der aus Fluor, Chlor, (C₁-C₄)-Alkyl
   oder (C₁-C₄)-Alkoxy bestehenden Gruppe, substituiert ist, (C₃-C₇)-Cycloalkylthio, wobei der Cycloalkylthiorest unsubstituiert ist oder durch einen oder mehrere Substituenten, ausgewählt aus der aus Fluor, Chlor, (C₁-C₄)-Alkyl oder (C₁-C₄)-Alkoxy bestehenden Gruppe, substituiert ist, und Phenyl oder 1-Naphthyl oder 2-Naphthyl oder ein fünf- oder sechsgliedriger heteroaromatischer Ring mit 1 bis 2 Heteroatomen, wobei die Heteroatome unabhängig voneinander ausgewählt sind, aus der Gruppe bestehend aus O oder N und wobei der Aryl- oder Heteroarylrest unsubstituiert ist oder durch einen oder mehrere Substituenten, ausgewählt aus der aus Fluor, Chlor, Brom, lod, (C₁-C₄)-Alkyl, (C₁-C₄)-Alkoxy oder (C₃-C₇)-Cycloalkyl oder (C₁-C₄)-Alkylthio bestehenden Gruppe, substituiert ist, und
   R^2" für
   (C₁-C₆)-Alkyl, wobei der Alkylrest unsubstituiert ist oder ganz oder teilweise mit Fluor substituiert ist, oder
   (C₃-C₇)-Cycloalkyl, wobei der Cycloalkylrest unsubstituiert ist oder ganz oder teilweise mit Fluor substituiert ist,
   R⁴ und R⁵ unabhängig voneinander jeweils für
   Wasserstoff,
   (C₁-C₆)-Alkyl, wobei der Alkylrest unsubstituiert ist oder durch einen oder mehrere Substituenten, ausgewählt aus der aus Fluor, Chlor, (C₁-C₄)-Alkoxy oder (C₃-C₇)-Cycloalkyl bestehenden Gruppe, substituiert ist,
   (C₁-C₆)-Alkoxy, wobei der Alkoxyrest verzweigt oder unverzweigt ist und unsubstituiert ist oder durch einen oder mehrere Substituenten, ausgewählt aus der aus Fluor, Chlor, (C₁-C₄)-Alkoxy oder (C₃-C₇)-Cycloalkyl bestehenden Gruppe, substituiert ist,
   stehen, und
   R⁸ für
   (C₁-C₆)-Alkyl, wobei der Alkylrest unsubstituiert ist oder ganz oder teilweise mit Fluor substituiert ist,
   (C₁-C₆)-Cycloalkyl, (C₁-C₆)-Alkenyl oder (C₁-C₆)-Alkoxyalkyl, wobei jeder der genannten Reste unsubstituiert ist oder ganz oder teilweise mit Fluor substituiert ist,
   steht, wobei
   ein 1,3-Dihydro-2H-indol-2-on der Formel (6-1)
   
   worin
   R^1a bis R^1d wie für Formel (4-1) definiert sind,
   R³ für Wasserstoff steht, und
   R⁷ für Wasserstoff steht, in einem
   ersten Schritt durch
   • Arylierung zu einem triazinylsubstituierten Oxindol der Formel (5-1)
     
     worin
     R^1a bis R^1d und R⁴ und R⁵ wie für die Formel (4-1) und R³ und R⁷ wie für die Formel (5-1) definiert sind,
     umgesetzt wird, und die Arylierungsprodukte der Formel (5-1) in einem
     zweiten Schritt durch
   • Sulfonylierung zu N-sulfonylsubstituierten 3-Triazinyloxindolen der Formel (2-1)
     
     worin R^1a bis R^1d, R² sowie R⁴ und R⁵ wie in Formel (4-1) und R³ wie für die Formel (5-1)definiert sind,
     umgesetzt werden, und die Sulfonylierungsprodukte der Formel (2-1) in einem
     dritten Schritt durch
   • oxidative Ringöffnung zu einem 2-(Triazinylcarbonyl)sulfonanilid der Formel (1-1)
     
     worin
     R^1a bis R^1d, R^2" sowie R⁴ und R⁵ wie für Formel (4-1) definiert sind,
     umgesetzt werden, und die Oxidationsprodukte der Formel (1-1) in einem
     vierten Schritt durch
   • Alkylierung zu einem N-Alkyl-N-[2-(1,3,5-triazin-2-ylcarbonyl)phenyl] alkansulfonamid der Formel (4-1)
     
     worin
     R^1a bis R^1d, R^2" , R⁴, R⁵ und R⁸ wie oben für Formel (4-1) definiert sind, umgesetzt werden, wobei als Alkylierungsreagenz
   • X- R⁸, wobei X für Chlor, Brom oder lod steht und R⁸ wie oben für Formel (4-1) definiert ist, oder
   • (R⁸)₂SO₄, worin R⁸ wie oben für Formel (4-1) definiert ist,
     eingesetzt wird.
   
   Die Sulfonylierung erfolgt in Gegenwart
   • einer in 1-Position substituierten Imidazol-Base, oder
   • eines Basen-Gemischs, das mindestens eine in 1-Position substituierte Imidazol-Base enthält.
   
   Besonders bevorzugte Imidazol-Basen sind 1-Methyl-1H-Imidazol, 1-Butyl-1H-Imidazol oder 1-Benzyl-1H-Imidazol, die einzeln oder im Gemisch eingesetzt werden können, wobei die Verwendung von 1-Methyl-1H-Imidazol ganz besonders bevorzugt ist.
2. B) Verfahren zur Herstellung von N-Alkyl-N-[2-(1,3,5-triazin-2-ylcarbonyl)phenyl] alkansulfonamiden der Formel (4-1) bei dem die als Edukt eingesetzten Verbindungen der Formel (6-1) in einem dem Verfahren zur Herstellung von Verbindungen der Formel (4-1) vorhergehenden Verfahrensschritt hergestellt werden, wobei ausgehend von einem 3-(Alkylsulfanyl)-1,3-dihydro-2H-indol-2-on der Formel (7-1),
   
   worin
   R^1a bis R^1d wie für Formel (4-1) definiert sind,
   R³ für Wasserstoff steht,
   R⁷ für Wasserstoff steht, und
   R⁶ ein unsubstituiertes oder substituiertes (C₁-C₁₄)-Alkyl, (C₃-C₇)-Cycloalkyl, Benzyl oder ein CH₂-C(O)O-(C₁-C₆)-Alkyl ist,
   durch
   • Reduktion zu einem 1,3-Dihydro-2H-indol-2-on (6-1)
     
     worin
     R^1a bis R^1d, R³ und R⁷ wie für Formel (7-1) definiert sind,
     umgewandelt wird.

The feasibility of the method summarized in Scheme 3 is disclosed in detail below. The reduction, which in Scheme 3 relates to the first reaction step of the overall five-step process, was subsequently treated as an independent precursor B). The process A) described in detail below thus comprises the steps of arylation, sulfonylation, oxidation and alkylation.

1. A) Process for the preparation of N-alkyl-N- [2- (1,3,5-triazin-2-ylcarbonyl) phenyl] alkanesulfonamides of the formula (4-1)
   
   wherein
   R ^1a to R ^{1d are} independently selected from the group consisting of hydrogen, fluorine, chlorine, bromine, iodine and from
   (C ₁ -C ₆ ) -alkyl, wherein the alkyl radical is unsubstituted or by one or more substituents selected from among fluorine, chlorine, (C ₁ -C ₄ ) -alkoxy or (C ₃ -C ₇ ) -cycloalkyl Group, is substituted,
   (C ₃ -C ₇ ) -cycloalkyl, wherein the cycloalkyl radical is unsubstituted or by one or more substituents selected from among fluorine, chlorine, (C ₁ -C ₄ ) -alkyl or (C ₃ -C ₇ ) -cycloalkyl or (C ₁ -C ₄ ) -alkoxy group, is substituted,
   (C ₁ -C ₆ ) -Alkoxy, wherein the alkoxy radical is unsubstituted or by one or more substituents selected from among fluorine, chlorine, (C ₁ -C ₄ ) -alkoxy
   or (C ₃ -C ₇ ) -cycloalkyl group, (C ₃ -C ₇ ) -cycloalkoxy, wherein the cycloalkoxy radical is unsubstituted or substituted by a
   or a plurality of substituents selected from the group consisting of fluorine, chlorine, (C ₁ -C ₄ ) -alkyl or (C ₁ -C ₄ ) -alkoxy, (C ₁ -C ₆ ) -alkylthio, wherein the alkylthio radical is unsubstituted or substituted by one or more substituents selected from fluoro, chloro, (C ₁ -C ₄ ) alkyl
   or (C ₁ -C ₄ ) -alkoxy group, (C ₃ -C ₇ ) -cycloalkylthio, wherein the cycloalkylthio radical is unsubstituted or substituted by one or more substituents selected from among fluorine, chlorine, (C ₁ -) C ₄ ) alkyl or (C ₁ -C ₄ ) alkoxy group, and phenyl or 1-naphthyl or 2-naphthyl or a five- or six-membered heteroaromatic ring having 1 to 2 heteroatoms, wherein the heteroatoms independently are selected from the group consisting of O or N and wherein the aryl or heteroaryl radical is unsubstituted or by one or more substituents selected from among fluorine, chlorine, bromine, iodine, (C ₁ -C ₄ ) -alkyl, ( C ₁ -C ₄ ) -alkoxy or (C ₃ -C ₇ ) -cycloalkyl or (C ₁ -C ₄ ) -alkylthio group, and
   R ^{2 "} for
   (C ₁ -C ₆ ) -alkyl, where the alkyl radical is unsubstituted or wholly or partly substituted by fluorine, or
   (C ₃ -C ₇ ) -cycloalkyl, where the cycloalkyl radical is unsubstituted or wholly or partly substituted by fluorine,
   R ⁴ and R ⁵ are each independently
   Hydrogen,
   (C ₁ -C ₆ ) -alkyl, wherein the alkyl radical is unsubstituted or by one or more substituents selected from among fluorine, chlorine, (C ₁ -C ₄ ) -alkoxy or (C ₃ -C ₇ ) -cycloalkyl Group, is substituted,
   (C ₁ -C ₆ ) -Alkoxy, wherein the alkoxy radical is branched or unbranched and is unsubstituted or by one or more substituents selected from among fluorine, chlorine, (C ₁ -C ₄ ) alkoxy or (C ₃ -C ₇ ) -cycloalkyl-substituted group, is substituted,
   stand, and
   R ⁸ for
   (C ₁ -C ₆ ) -alkyl, where the alkyl radical is unsubstituted or wholly or partly substituted by fluorine,
   (C ₁ -C ₆ ) -cycloalkyl, (C ₁ -C ₆ ) -alkenyl or (C ₁ -C ₆ ) -alkoxyalkyl, where each of the radicals mentioned is unsubstituted or is wholly or partly substituted by fluorine,
   stands, where
   a 1,3-dihydro-2H-indol-2-one of the formula (6-1)
   
   wherein
   R ^1a to R ^{1d are} as defined for formula (4-1),
   R ^{3 is} hydrogen, and
   R ^{7 is} hydrogen, in one
   first step through
   • Arylation to a triazinyl-substituted oxindole of the formula (5-1)
     
     wherein
     R ^1a to R ^1d and R ⁴ and R ^{5 are} as defined for the formula (4-1) and R ³ and R ^{7 are} as defined for the formula (5-1),
     is reacted, and the arylation products of the formula (5-1) in one
     second step through
   • Sulfonylation to N-sulfonyl-substituted 3-triazinyloxindoles of the formula (2-1)
     
     wherein R ^1a to R ^1d , R ² and R ⁴ and R ^{5 are} as defined in formula (4-1) and R ³ as defined for the formula (5-1),
     be reacted, and the sulfonylation of the formula (2-1) in one
     third step through
   • oxidative ring opening to a 2- (triazinylcarbonyl) sulfonanilide of formula (1-1)
     
     wherein
     R ^1a to R ^1d , R ^{2 "} and R ⁴ and R ^{5 are} as defined for formula (4-1),
     be reacted, and the oxidation products of the formula (1-1) in one
     fourth step through
   • Alkylation to an N-alkyl-N- [2- (1,3,5-triazin-2-ylcarbonyl) phenyl] alkanesulfonamide of the formula (4-1)
     
     wherein
     R ^1a to R ^1d , R ^{2 "} , R ⁴ , R ⁵ and R ^{8 are} as defined above for formula (4-1), being reacted as alkylating reagent
   • X-R ⁸ , wherein X is chlorine, bromine or iodine and R ^{8 is} as defined above for formula (4-1), or
   • (R ⁸ ) ₂ SO ₄ , wherein R ^{8 is} as defined above for formula (4-1),
     is used.
   
   The sulfonylation takes place in the presence
   • a substituted in 1-position imidazole base, or
   • a base mixture containing at least one 1-substituted imidazole base.
   
   Particularly preferred imidazole bases are 1-methyl-1H-imidazole, 1-butyl-1H-imidazole or 1-benzyl-1H-imidazole, which can be used alone or in admixture, the use of 1-methyl-1H-imidazole is very particularly preferred.
2. B) Process for the preparation of N-alkyl-N- [2- (1,3,5-triazin-2-ylcarbonyl) phenyl] alkanesulfonamides of the formula (4-1) in which the compounds of the formula (6) used as starting material 1) in a process step preceding the process for the preparation of compounds of the formula (4-1), starting from a 3- (alkylsulfanyl) -1,3-dihydro-2H-indol-2-one of the formula (7) 1),
   
   wherein
   R ^1a to R ^{1d are} as defined for formula (4-1),
   R ^{3 is} hydrogen,
   R ^{7 is} hydrogen, and
   R ^{6 is} an unsubstituted or substituted (C ₁ -C ₁₄ ) -alkyl, (C ₃ -C ₇ ) -cycloalkyl, benzyl or is a CH ₂ -C (O) O- (C ₁ -C ₆ ) -alkyl,
   by
   • Reduction to a 1,3-dihydro-2H-indol-2-one (6-1)
     
     wherein
     R ^1a to R ^1d , R ³ and R ^{7 are} as defined for formula (7-1),
     is converted.

1. a) eine Verbindung der Formel (7-1) in einem polaren Lösungsmittel gelöst oder suspendiert wird,
2. b) der Lösung oder der Suspension ein schwefelhaltiges Salz zugesetzt wird, und
3. c) das Reaktionsgemisch bei einer Temperatur, die maximal der Siedetemparatur des polaren Lösungsmittels entspricht, unter Rückfluss erwärmt wird.

When the reduction is

1. a) dissolving or suspending a compound of the formula (7-1) in a polar solvent,
2. b) a sulfur-containing salt is added to the solution or suspension, and
3. c) the reaction mixture is heated at a temperature which corresponds at most to the boiling point of the polar solvent, under reflux.

Particularly preferred sulfur-containing salts are sodium salts selected from the group consisting of sodium bisulfite, sodium sulfite, sodium thionite, sodium dithionite and sodium thiosulfate.

The herbicides (see WO 2007/031208 A2 ) and fungicides (see WO 2006/008159 A1 ) Effect of N-alkyl-N- [2- (1,3,5-triazin-2-ylcarbonyl) phenyl] alkanesulfonamides of the formula (4-1) is, as already mentioned, known for a long time.

Thus, it is demonstrated by Scheme 3 and the methods A) and B) that triazinyl-substituted oxindoles of the formula (3) are suitable as intermediates for the preparation of crop protection agents, in particular herbicides and fungicides.

The invention therefore also relates to the use of the compounds according to the invention of the formulas (3) or salts thereof (3 ") for the production of active ingredients from agriculture or intermediates for the production of fine chemicals and active ingredients from agriculture, especially pesticides.

Preference is given to the use of compounds of the formula (3) or salts thereof (3 ") as intermediates for the preparation of N- [2- (1,3,5-triazin-2-ylcarbonyl) phenyl] alkylsulfonamides.

EXAMPLES

The following examples illustrate the invention in more detail.

In the following examples, amounts are by weight unless otherwise specifically defined (in the description, by weight,% by weight was used by analogy). For units of measure, physical quantities and the like, common abbreviations are used, for example h = hour (s), mpt = melting point (m.p.), l = liter, ml = milliliter, g = gram, min = minute (n), in vacuo = "in vacuum" = under reduced pressure, d. Th. = Percent yield according to theory.

Example 1: Preparation of 3- (4,6-dimethoxy-1,3,5-triazin-2-yl) -7-fluoro-1,3-dihydro-2H-indol-2-one

Option A:

7-fluoro-1,3-dihydro-2H-indol-2-one (100 g) is initially charged in 600 ml of N, N-dimethylacetamide and cooled to about 0 ° C. with ice / methanol cooling. A solution of potassium hydroxide (43.2 g) and potassium carbonate (143 g) in 600 ml of water is added and stirred briefly. Subsequently, 2-chloro-4,6-dimethoxy-1,3,5-triazine (140.8 g) was added and rinsed with 100 ml of water and N, N-dimethylacetamide. The cooling bath is removed, the batch is heated to about 30 ° C. It is stirred for 18 hours at room temperature. After adding 150 ml of toluene, dilute with hydrochloric acid (about 700 ml) to pH 3-4 and add a little defoamer (Fluowet PL 80). The solid is filtered off with suction, three times each 250 ml of water and washed twice with 250 ml of heptane and dried in vacuo at 55 ° C. The title compound is obtained as a solid in a purity of 96.6% (187.5 g, 95% of theory).
LC-MS: M + H = 291 (100%).
1H-NMR (400 MHz, DMSO-D ₆ ): δ (ppm) = 11.37 (s, 1H), 7.64 (d, 1H), 6.97 (dt, 1H), 6.86 (dd, 1H), 4.05 (s, 6H).

Variant B:

7-Fluoro-1,3-dihydro-2H-indol-2-one (50 g) is initially charged in 400 ml of acetone and potassium hydroxide (21.5 g) is added. Subsequently, 2-chloro-4,6-dimethoxy-1,3,5-triazine (70.06 g) is added rinsing with 100 ml of acetone. The reaction mixture is stirred for one hour at reflux, the heat bath removed, and potassium hydroxide (21.5 g) added portionwise. The mixture is then stirred for 2 hours at reflux. The batch cooled to 25 ° C, ten percent hydrochloric acid (140 ml) was added, diluted with 250 ml of water and stirred for one hour. The solid is filtered off, washed twice with 100 ml of water / acetone (3: 1) and dried in vacuo at 50 ° C. The title compound is obtained as a solid in a purity of 96.2% (80.09 g, 81% of theory). The NMR signals of the product are in agreement with the signals of the product obtained according to Variant A.

Variant C:

7-Fluoro-1,3-dihydro-2H-indol-2-one (12 g) and 2-chloro-4,6-dimethoxy-1,3,5-triazine (16.5 g) are initially charged at room temperature in 160 ml of formamide and potassium carbonate (24.3 g) in three equal portions over 1.5 hours. The reaction mixture is stirred for 4 to 5 hours at room temperature. The mixture is added to 500 ml of water and adjusted to pH 3 with dilute hydrochloric acid. The solid is filtered off with suction and washed with water, then with acetonitrile, and dried in vacuo. The title compound is obtained as a solid in an HPLC purity of 98% area (93.0 g, 80% of theory). The NMR signals of the product are in agreement with the signals of the product obtained according to Variant A.

Variant D:

7-Fluoro-1,3-dihydro-2H-indol-2-one (60 g) and 2-chloro-4,6-dimethoxy-1,3,5-triazine (94.6 g) are initially charged in 315 ml of THF and cooled to 5 ° C. Under ice cooling, a solution of potassium hydroxide (58.1g) in 105 ml of water within 2 hours at an internal temperature of 0-15 ° C was added and stirred for 4 hours. The solid is filtered off, washed with water (twice 150 ml) and dried in vacuo. The title compound is obtained as a solid in a purity of 98.2% (21.1 g, 91% of theory). The NMR signals of the product are in agreement with the signals of the product obtained according to Variant A.

Variant E:

7-Fluoro-1,3-dihydro-2H-indol-2-one (30g) and 2-chloro-4,6-dimethoxy-1,3,5-triazine (43.9g) are added at 60 ° C presented in acetonitrile and sodium hydroxide (16.8 g) in four equal portions within 40 min. The mixture was stirred for a further 90 min at this temperature and then cooled to 40 ° C. Hydrochloric acid (20%, 42 g) and water (160 g) were added. After a further 30 minutes, the resulting suspension was filtered and the filter residue was washed with acetonitrile. After drying in vacuo (50 ° C., <200 mbar), the title compound was obtained as a solid with an HPLC purity of 96.9% (48.0 g, 85% of theory). The NMR signals of the product are in agreement with the signals of the product obtained according to Variant A.

Variant F:

7-Fluoro-1,3-dihydro-2H-indol-2-one (10 g, 1 eq.) Is charged in 100 ml of THF and 100 ml of N, N-dimethylformamide at room temperature under nitrogen and sodium hydride (2.63 g, 60 % in mineral oil, 1 eq.). After stirring for 30 minutes, 2-chloro-4,6-dimethoxy-1,3,5-triazine (4.72 g, 0.4 eq.) Is added in one portion. It is stirred for 10 min at 35 ° C and 2 hours at 80 ° C. The mixture is cooled and concentrated in vacuo (50 ° C bath temperature, 10 mbar). To the residue is added 200 ml of water and adjusted to pH 3-4 with hydrochloric acid. The precipitated solid is filtered off, the filtrate contains virtually no product by HPLC. The filter residue is washed with water (50 ml), washed with water until wet with 75 ml of acetonitrile, filtered off with suction, washed with acetonitrile and dried in vacuo. The title compound is obtained as a solid in an HPLC purity of 97% area (7.62 g, 39% of theory based on the 7-fluoro-1,3-dihydro-2H-indol-2-one or 97 used % of theory, based on the 2-chloro-4,6-dimethoxy-1,3,5-triazine used). The NMR signals of the product are in agreement with the signals of the product obtained according to Variant A.

Variant G:

7-Fluoro-1,3-dihydro-2H-indol-2-one (10g; 1 eq.) And 2-chloro-4,6-dimethoxy-1,3,5-triazine (14.1g; 1.2 eq.) are implemented analogously to Example 1 variant F. The title compound is obtained as a solid in an HPLC purity of 97% area (7.65 g, 39% of theory based on the 7-fluoro-1,3-dihydro-2H-indol-2-one used). The NMR signals of the product are in agreement with the signals of the product obtained according to Variant A.

Variant H (Implementation analogous to Organic Letters (2010) 2306 Examples in Table 4 (Supplement Page S-12 General Procedure):

7-Fluoro-1,3-dihydro-2H-indol-2-one (2.5 g; 1 eq.), 2-chloro-4,6-dimethoxy-1,3,5-triazine (3.5 g; 1 , 2 eq.) And cesium carbonate (5.6 g, 1 eq.) Are introduced under nitrogen and 95 ml of N, N-dimethylformamide (water content <0.1%) was added. The mixture is heated to 65 ° C and stirred for 5 hours at 65 ° C under nitrogen. HPLC analysis (detection at 210 nm, data in area percent, solvent signal is not integrated) shows 16% of 7-fluoro-1,3-dihydro-2H-indol-2-one, 19% of the title compound (3- (4, 6-dimethoxy-1,3,5-triazin-2-yl) -7-fluoro-1,3-dihydro-2H-indol-2-one), 57% of a major minor component (or mixture of major major minor components) and other minor ones secondary components. The reaction is cooled to room temperature and added to 200 ml of saturated ammonium chloride solution. Ethyl acetate is added until two clear phases are formed (Total 2900 ml), the phases were separated, the organic phase washed with water (2 times 150 ml) and 150 ml of sodium chloride solution and dried over magnesium sulfate. The solvent is removed in vacuo, precipitating a solid. The solid is filtered off and washed with a little ethyl acetate. This gives 1.92 g of a mixture which, according to HPLC analysis (detection at 210 nm, data in area percent), consists of 56% (22% of theory) of the title compound and 43% of a secondary component. LC-MS of the mixture indicates the presence of the title compound (M + H = 291) and a minor component of the mass of 429 (M + H = 430), which is likely a doubly arylated product. The identity of the title compound contained in the product mixture can be confirmed by stocking up the reaction mixture with authentic material prepared according to Example 1 variant A, and comparing the UV absorptions, as well as by NMR spectroscopy of the mixture.

The filtrate is concentrated in vacuo, giving 3.6 g of residue which still contains DMF. HPLC analysis (detection at 210 nm, data in area percent, solvent signal is not integrated) of the residue shows 19% of 7-fluoro-1,3-dihydro-2H-indol-2-one, 1% of the title compound, 68% of a Mixture of two major minor components and minor minor components. LC-MS of the residue indicates the presence of the title compound (M + H = 291, 4%) and two minor components of the mass of 429 (M + H = 430, 19% and 49%), presumably arylating twice Products is.

Example 2: Preparation of 3- (4,6-dimethoxy-1,3,5-triazin-2-yl) -1,3-dihydro-2H-indol-2-one

Option A:

1,3-Dihydro-2H-indol-2-one (3.0 g) and 2-chloro-4,6-dimethoxy-1,3,5-triazine (7.52 g) are reacted analogously to Example 1 variant C. The title compound is obtained as a solid in an HPLC purity of 91% area (4.79 g, 73% of theory).
LC-MS: M + H = 273 (91.8%).
1 H-NMR (400 MHz, DMSO-D ₆ ): δ (ppm) = 10.96 (s, 1H), 7.78-7.84 (m, 1H), 6.95-7.04 (m, 3H), 4.04 (s, 6H).

Variant B:

1,3-Dihydro-2H-indol-2-one (0.80 g, 1 eq.) Is charged in 8 mL of THF and 8 mL of N, N-dimethylformamide at room temperature under nitrogen and sodium hydride (0.24 g, 60% in Mineral oil, 1 eq.). After stirring for 30 minutes, 2-chloro-4,6-dimethoxy-1,3,5-triazine (0.42 g, 0.4 eq.) Is added in one portion. It is stirred for 2 hours at room temperature. The mixture is cooled and concentrated in vacuo (40 ° C bath temperature). To the residue is added 25 ml of water and adjusted to pH 3-4 with hydrochloric acid. The precipitated solid is filtered off with suction, the filtrate contains virtually no product after HPLC. The filter residue is washed with water, moistened with 10 ml of acetonitrile and filtered with suction. The title compound is obtained as a solid in an HPLC purity of 90% area (0.61 g, 34% of theory based on the 1,3-dihydro-2H-indol-2-one used or 84% of theory relative to the 2-chloro-4,6-dimethoxy-1,3,5-triazine used). The NMR signals of the product are in agreement with the signals of the product obtained according to Variant A.

Variant C:

1,3-dihydro-2H-indol-2-one (0.80 g, 1 eq.) And 2-chloro-4,6-dimethoxy-1,3,5-triazine (1.27 g, 1.2 eq. ) are implemented analogously to Example 1 variant F. The title compound is obtained as a solid in an HPLC purity of 78% area (0.59 g, 30% of theory based on the 1,3-dihydro-2H-indol-2-one used). The NMR signals of the product are in agreement with the signals of the product obtained according to Variant A.

Example 3: Preparation of 3- (4,6-dimethoxy-1,3,5-triazin-2-yl) -5,7-difluoro-1,3-dihydro-2H-indol-2-one

5,7-Difluoro-1,3-dihydro-2H-indol-2-one (1.69g) and 2-chloro-4,6-dimethoxy-1,3,5-triazine (2.13g) are prepared analogously Example 1 Variant A implemented. The title compound is obtained as a solid in an HPLC purity of 93% area (2.82 g, 85% of theory).
LC-MS: M + H = 309 (97%).
1 H-NMR (400 MHz, DMSO-D ₆ ): δ (ppm) = 11.42 (s, 1H), 7.35 (dd, 1H), 6.86 (dt, 1H), 4.04 (s, 6H).

Example 4: Preparation of 3- (4,6-dimethoxy-1,3,5-triazin-2-yl) -7-chloro-1,3-dihydro-2H-indol-2-one

7-Chloro-1,3-dihydro-2H-indol-2-one (101.5 g) and 2-chloro-4,6-dimethoxy-1,3,5-triazine (152 g) are analogous to Example 1 variant A. implemented. The title compound is obtained as a solid in an HPLC purity of 99% area (181.9 g, 97% of theory).
LC-MS: M + H = 307 (96.7%).
1 H-NMR (400 MHz, DMSO-D ₆ ): δ (ppm) = 11.39 (s, 1H), 7.77 (d, 1H), 6.98-7.06 (m, 2H), 4.05 (s, 6H).

Example 5: Preparation of 3- (4,6-dimethoxy-1,3,5-triazin-2-yl) -5-fluoro-1,3-dihydro-2H-indol-2-one

5-fluoro-1,3-dihydro-2H-indol-2-one (10 g) and 2-chloro-4,6-dimethoxy-1,3,5-triazine (15.5 g) are analogous to Example 1 variant A. implemented. The title compound is obtained as a solid in an HPLC purity of 92% area (19 g, 91% of theory).
LC-MS: M + H = 291 (90%).
1H-NMR (400 MHz, DMSO-D ₆ ): δ (ppm) = 11.06 (s, 1H), 7.53 (dd, 1H), 6.95 (dd, 1H), 6.82 (dt, 1H), 4.06 (s, 6H).

Example 6: Preparation of 3- (4,6-dimethoxy-1,3,5-triazin-2-yl) -7-methoxy-1,3-dihydro-2H-indol-2-one

7-Methoxy-1,3-dihydro-2H-indol-2-one (1.24 g) and 2-chloro-4,6-dimethoxy-1,3,5-triazine (1.84 g) are prepared analogously to Example 1 Variant A implemented. The title compound is obtained as a solid in an HPLC purity of 87% area (1.04 g, 43% of theory).
LC-MS: MH = 301 (84%).
1H-NMR (400 MHz, DMSO-D ₆ ): δ (ppm) = 11.36 (s, 1H), 7.52 (d, 1H), 6.96 (t, 1H), 6.71 (d, 1H), 4.04 (s, 6H), 3.85 (s, 3H).

Example 7: Preparation of 3- (4,6-dimethoxy-1,3,5-triazin-2-yl) -5-methoxy-1,3-dihydro-2H-indol-2-one

5-Methoxy-1,3-dihydro-2H-indol-2-one (1.59 g) and 2-chloro-4,6-dimethoxy-1,3,5-triazine (1.97 g) are prepared analogously to Example 1 Variant A implemented. The title compound is obtained as a solid in an HPLC purity of 92% area (1.39 g, 53% of theory).
LC-MS: M + H = 303 (94%).
1H-NMR (400 MHz, DMSO-D ₆ ): δ (ppm) = 10.89 (s, 1H), 7.43 (d, 1H), 6.89 (d, 1H), 6.61 (dd, 1H), 4.06 (s, 6H), 3.74 (s, 3H).

Example 8: Preparation of 7-fluoro-3- (4-methoxy-6-methyl-1,3,5-triazin-2-yl) -1,3-dihydro-2H-indol-2-one

7-Fluoro-1,3-dihydro-2H-indol-2-one (3.05g) and 2-chloro-4-methoxy-6-methyl-1,3,5-triazine (6.59g) are prepared analogously Example 1 Variant A implemented. The title compound is obtained as a solid in an HPLC purity of 85% area (4.73 g, 73% of theory).
LC-MS: M + H = 275 (72%).
1 H-NMR (400 MHz, DMSO-D ₆ ): δ (ppm) = 11.02 (s, 1H), 7.59 (d, 1H), 6.91-6.98 (m, 1H), 6.85 (t, 1H), 4.06 ( s, 3H), 2.46 (s, 3H).

Example 9: Preparation of 3- (4,6-Diethoxy-1,3,5-triazin-2-yl) -7-fluoro-1,3-dihydro-2H-indol-2-one

7-Fluoro-1,3-dihydro-2H-indol-2-one (1.0 g) is initially charged in 10 ml of N, N-dimethylacetamide. A solution of potassium carbonate (1.8 g) and potassium hydroxide (0.3 g) in 10 ml of water is added and the mixture is stirred briefly. Subsequently, a solution of 2-chloro-4,6-diethoxy-1,3,5-triazine (3.0 g, about 50% purity) in 10 ml N, N-dimethylacetamide and 10 ml of water. From the clear yellow solution, a solid separates out. The reaction is stirred at room temperature and additional 2-chloro-4,6-diethoxy-1,3,5-triazine (1 g, about 50% purity) is added in two portions after 2 and 18 hours, respectively. The mixture is stirred for 3 hours at 30 ° C, 10 ml of toluene, adjusted with hydrochloric acid (10%) to pH 1-2 and stirred for 30 min. The solid is filtered off, washed twice alternately with water and heptane and dried. The title compound is obtained as a solid in an HPLC purity of 99% area (1.53 g, 72% of theory).
LC-MS: M + H = 319 (86%).
1H-NMR (400 MHz, DMSO-D ₆ ): δ (ppm) = 11.3 (s, 1H), 7.59 (d, 1H), 6.96 (dd, 1H), 6.93-7.00 (m, 1H), 4.50 ( q, 4H), 1.37 (t, 6H).

Example 10: Preparation of 2 - [(4,6-dimethoxy-1,3,5-triazin-2-yl) oxy] -3-phenyl-1H-indole (carried out analogously to Organic Letters (2010) 2306 Examples in Table 4 (Supplement Page S-12 General Procedure):

3-phenyl-1,3-dihydro-2H-indol-2-one (0.25 g, 1 eq.), 2-chloro-4,6-dimethoxy-1,3,5-triazine (0.20 g, 1 eq.) and cesium carbonate (0.37 g, 1 eq.) Are introduced and 20 ml of N, N-dimethylformamide (water content <0.1%) was added. The mixture is stirred for 90 min at 23 ° C. HPLC analysis (detection at 210 nm, data in area percent, solvent signal is not integrated) shows 3% 3-phenyl-1,3-dihydro-2H-indol-2-one, 1.5% 2-chloro-4, 6-dimethoxy-1,3,5-triazine, 68% of a major product and minor minor components. The mixture is added to 100 ml of water and adjusted to pH 4 with dilute hydrochloric acid. The precipitated solid is filtered off and washed with water. You get a mixture, which according to HPLC analysis (detection at 210 nm, data in area percent) consists of 71% of a main product (0.37 g, 66% of theory). 100 mg of the mixture are purified by column chromatography (eluent ethyl acetate and n-heptane 1: 1) and the combined product fractions are concentrated in vacuo. The reaction product is obtained as a colorless solid in an HPLC purity of 93% area. Structural analysis by 2D NMR confirms that it is not the 3-position arylated product (3- (4,6-dimethoxy-1,3,5-triazin-2-yl) -3-phenyl-1,3 -dihydro-2H-indol-2-one) but the O-arylated product (2 - [(4,6-dimethoxy-1,3,5-triazin-2-yl) oxy] -3-phenyl-1H indole).
LC-MS: M + H = 349 (96%).
1H-NMR (600 MHz, CDCl _3): δ (ppm) = 8.95 (s, broad, 1H), 7.82 (d, 1H), 7.65 (dd, 2H), 7:41 (t, 2H), 7:37 (d, 1H), 7.24 (q, 2H), 7.19 (t, 1H), 3.98 (s, 6H).

Claims (18)

1. A process for the preparation of compounds of formula (3)

   

   in which
   R^1a to R^1d, independently of one another, are selected from the group consisting of hydrogen, fluorine, chlorine, bromine, iodine, and also from
   (C₁-C₆)-alkyl, where the alkyl radical is unsubstituted or is substituted by one or more substituents selected from the group consisting of fluorine, chlorine, (C₁-C₄) -alkoxy or (C₃-C₇)-cycloalkyl,
   (C₃-C₈)-cycloalkyl, where the cycloalkyl radical is unsubstituted or is substituted by one or more substituents selected from the group consisting of fluorine, chlorine, (C₁-C₄)-alkyl or (C₃-C₇)-cycloalkyl or (C₁-C₄)-alkoxy,
   (C₁-C₆)-alkoxy, where the alkoxy radical is unsubstituted or is substituted by one or more substituents selected from the group consisting of fluorine, chlorine, (C₁-C₄)-alkoxy or (C₃-C₇)-cycloalkyl,
   (C₃-C₇)-cycloalkoxy, where the cycloalkoxy radical is unsubstituted or is substituted by one or more substituents selected from the group consisting of fluorine, chlorine, (C₁-C₄)-alkyl or (C₁-C₄)-alkoxy,
   (C₁-C₆)-alkylthio, where the alkylthio radical is unsubstituted or is substituted by one or more substituents selected from the group consisting of fluorine, chlorine, (C₁-C₄)-alkyl or (C₁-C₉)-alkoxy, and also from
   (C₃-C₇)-cycloalkylthio, where the cycloalkylthio radical is unsubstituted or is substituted by one or more substituents selected from the group consisting of fluorine, chlorine, (C₁-C₄)-alkyl or (C₁-C₄)-alkoxy, and also from
   phenyl or 1-naphthyl or 2-naphthyl or a five- or six-membered heteroaromatic ring having 1 to 2 heteroatoms, where the heteroatoms, independently of one another, are selected from the group consisting of O or N and where the aryl or heteroaryl radical is unsubstituted or is substituted by one or more substituents selected from the group consisting of fluorine, chlorine, bromine, iodine, (C₁-C₄)-alkyl, (C₁-C₄) -alkoxy or (C₃-C₇) -cycloalkyl or (C₁-C₄)-alkylthio, and
   R² is
   hydrogen,
   (C₁-C₆)-alkyl, where the alkyl radical is unsubstituted or is substituted by one or more substituents selected from the group consisting of fluorine, chlorine, (C₁-C₄)-alkoxy or (C₃-C₇)-cycloalkyl, or
   benzyl, where the benzyl is unsubstituted or is substituted by one or more substituents selected from the group consisting of fluorine, chlorine, bromine, iodine, nitro, (C₁-C₄) -alkyl, (C₁-C₄) - alkoxy or (C₃-C₇)-cycloalkyl or (C₁-C₄)-alkylthio and also from COOR^a, in which R^a is a (C₁-C₄)-alkyl, and -CONR^b'R^b" or -CONHR^b", in which R^b' and R^b" are each independently of one another a (C₁-C₄)-alkyl, where in each case two substituents on the N atom together optionally form an unsubstituted or substituted ring,
   R³ is hydrogen or methyl,
   R⁴ and R⁵, independently of one another, are in each case
   hydrogen,
   (C₁-C₆)-alkyl, where the alkyl radical is unsubstituted or is substituted by one or more substituents selected from the group consisting of fluorine, chlorine, (C₁-C₄)-alkoxy or (C₃-C₇)-cycloalkyl,
   (C₁-C₆)-alkoxy, where the alkoxy radical is unsubstituted or is substituted by one or more substituents selected from the group consisting of fluorine, chlorine, (C₁-C₄)-alkoxy or (C₃-C₇)-cycloalkyl,
   where an oxindole (1)

   

   in which
   R^1a to R^1d and R² and R³ are as defined in formula (3), is reacted in a solvent with a triazine (2)

   

   in which
   R⁴ and R⁵ are as defined in formula (3), and
   X, as leaving group, is Cl, Br, I, alkoxy, alkylsulfonyl, (alkylsulfonyl)oxy, haloalkylsulfonyl, phenylsulfonyl or toluene-4-sulfonyl,
   which comprises carrying out the reaction in the presence of

   - potassium carbonate or sodium carbonate,

   - lithium hydroxide, sodium hydroxide, potassium hydroxide, barium hydroxide or tert-alkylammonium hydroxide,

   - potassium phosphate (K₃PO₄), potassium hydrogenphosphate (K₂HPO₄) or sodium phosphate or

   - in a mixture comprising at least two of the aforementioned bases.
2. The process for the preparation of compounds of formula (3) as claimed in claim 1, wherein R^1a to R^1d, independently of one another, are selected from the group consisting of hydrogen, fluorine, chlorine, bromine, iodine, and also from
   (C₁-C₆)-alkyl, where the alkyl radical is unsubstituted or is substituted by one or more substituents selected from the group consisting of fluorine and chlorine, and
   (C₃-C₇)-cycloalkyl, where the cycloalkyl radical is unsubstituted or is substituted by one or more substituents selected from the group consisting of fluorine and chlorine, (C₁-C₄) -alkyl or (C₃-C₇)-cycloalkyl or (C₁-C₄)-alkoxy.
3. The process for the preparation of compounds of formula (3) as claimed in claim 2, wherein R^1a to R^1d, independently of one another, are selected from the group consisting of fluorine, chlorine, trifluoromethyl, trifluoromethoxy and methoxy.
4. The process for the preparation of compounds of formula (3) as claimed in claim 3, wherein R^1a is fluorine or chlorine.
5. The process for the preparation of compounds of formula (3) as claimed in one of the preceding claims,
   wherein
   R² is

   - hydrogen, or is in each case

   - unsubstituted methyl, ethyl and benzyl.
6. The process for the preparation of compounds of formula (3) as claimed in claim 5, wherein R² is hydrogen.
7. The process for the preparation of compounds of formula (3) as claimed in one of the preceding claims, wherein R⁴ and R⁵, independently of one another, are

   - unsubstituted (C₁-C₄)-alkyl, and

   - unsubstituted (C₁-C₄)-alkoxy.
8. The process for the preparation of compounds of formula (3) as claimed in one of the preceding claims, wherein X is chlorine.
9. The process for the preparation of compounds of formula (3) as claimed in one of the preceding claims, wherein the reaction of the starting materials is carried out in

   - a polar or

   - a nonpolar solvent, or

   - a mixture of a polar or nonpolar solvent.
10. The process for the preparation of compounds of formula (3) as claimed in one of the preceding claims, wherein the reaction takes place under anhydrous conditions in the presence of the bases mentioned in claim 1.
11. The process for the preparation of compounds of formula (3) as claimed in one of the preceding claims, wherein 1.1 to 1.4 equivalents of the triazine (2) are added to one equivalent of the oxindole (1).
12. The process for the preparation of compounds of formula (3) as claimed in one of the preceding claims, wherein the addition of the starting materials takes place in one portion or equally dosed over a period of up to 24 hours.
13. The process for the preparation of compounds of formula (3) as claimed in one of the preceding claims, wherein the reaction of the starting materials is carried out at a temperature in the range from -20° to 150°C.
14. A compound of formula (3)

    

    and salts thereof (3")

    

    in which
    R^1a to R^1d, independently of one another, are selected from the group consisting of hydrogen, fluorine, chlorine, bromine, iodine, and also from
    (C₁-C₆)-alkyl, where the alkyl radical is unsubstituted or is substituted by one or more substituents selected from the group consisting of fluorine, chlorine, (C₁-C₄)-alkoxy or (C₃-C₇)-cycloalkyl,
    (C₃-C₈)-cycloalkyl, where the cycloalkyl radical is unsubstituted or is substituted by one or more substituents selected from the group consisting of fluorine, chlorine, (C₁-C₄) -alkyl or (C₃-C₇)-cycloalkyl or (C₁-C₄)-alkoxy,
    (C₁-C₆)-alkoxy, where the alkoxy radical is unsubstituted or is substituted by one or more substituents selected from the group consisting of fluorine, chlorine, (C₁-C₄)-alkoxy or (C₃-C₇)-cycloalkyl,
    (C₃-C₇)-cycloalkoxy, where the cycloalkoxy radical is unsubstituted or is substituted by one or more substituents selected from the group consisting of fluorine, chlorine, (C₁-C₄)-alkyl or (C₁-C₄)-alkoxy,
    (C₁-C₆)-alkylthio, where the alkylthio radical is unsubstituted or is substituted by one or more substituents selected from the group consisting of fluorine, chlorine, (C₁-C₄)-alkyl or (C₁-C₄)-alkoxy,
    (C₃-C₇)-cycloalkylthio, where the cycloalkylthio radical is unsubstituted or is substituted by one or more substituents selected from the group consisting of fluorine, chlorine, (C₁-C₄)-alkyl or (C₁-C₄)-alkoxy, and also from
    phenyl or 1-naphthyl or 2-naphthyl or a five- or six-membered heteroaromatic ring having 1 to 2 heteroatoms, where the heteroatoms, independently of one another, are selected from the group consisting of O or N and where the aryl or heteroaryl radical is unsubstituted or is substituted by one or more substituents selected from the group consisting of fluorine, chlorine, bromine, iodine, (C₁-C₄) -alkyl, (C₁-C₄) -alkoxy or (C₃-C₇)-cycloalkyl or (C₁-C₄)-alkylthio, and
    R² is
    hydrogen,
    (C₁-C₆)-alkyl, where the alkyl radical is unsubstituted or is substituted by one or more substituents selected from the group consisting of fluorine, chlorine, (C₁-C₄)-alkoxy or (C₃-C₇)-cycloalkyl, or
    benzyl, where the benzyl is unsubstituted or is substituted by one or more substituents selected from the group consisting of fluorine, chlorine, bromine, iodine, nitro, (C₁-C₄)-alkyl, (C₁-C₄)-alkoxy or (C₃-C₇)-cycloalkyl or (C₁-C₄)-alkylthio and also from COOR^a, in which R^a is a (C₁-C₄)-alkyl, and -CONR^b'R^b" or -CONHR^b", in which R^b' and R^b" are each independently of one another a (C₁-C₄)-alkyl, where in each case two substituents on the N atom together optionally form an unsubstituted or substituted ring,
    R3 is
    Hydrogen or methyl,
    R⁴ and R⁵, independently of one another, are in each case
    hydrogen,
    (C₁-C₆)-alkyl, where the alkyl radical is unsubstituted or is substituted by one or more substituents selected from the group consisting of fluorine, chlorine, (C₁-C₄)-alkoxy or (C₃-C₇)-cycloalkyl,
    (C₁-C₆)-alkoxy, where the alkoxy radical is unsubstituted or is substituted by one or more substituents selected from the group consisting of fluorine, chlorine, (C₁-C₄)-alkoxy or (C₃-C₇)-cycloalkyl,
    where, in the salts of formula (3''),
    M is Li, Na, K, N(R^c)₄, where R^c = H or C_1-C₆ alkyl, Cs, Ba, Mg, Ca and Zn, and the number of counter ions M⁺ is governed by the particular charge such that an overall neutral compound of formula (3") is formed.
15. The use of a compound of formula (3) or salts thereof (3") as claimed in claim 14 for producing crop protection agents.
16. The use of a compound of formula (3) or salts thereof as claimed in claim 14 for producing herbicides or intermediates for producing herbicides.
17. The use of a compound of formula (3) or salts thereof as claimed in claim 14 for producing N-[2-(1,3,5-triazin-2-ylcarbonyl)phenyl]alkylsulfonamides.
18. The use of a compound of formula (3) or salts thereof as claimed in claim 14 for producing N-alkyl-N-[2-(1,3,5-triazin-2-ylcarbonyl)-phenyl]alkylsulfonamides.